PT - JOURNAL ARTICLE AU - Rieko Kojima AU - Yuriko Kakimoto AU - Manatsu Shinmyo AU - Kazuo Kurokawa AU - Akihiko Nakano AU - Toshiya Endo AU - Yasushi Tamura TI - A non-canonical unfolded protein response pathway and mitochondrial dynamics control the number of ER-mitochondria contact sites AID - 10.1101/684753 DP - 2019 Jan 01 TA - bioRxiv PG - 684753 4099 - http://biorxiv.org/content/early/2019/06/27/684753.short 4100 - http://biorxiv.org/content/early/2019/06/27/684753.full AB - Mitochondria maintain their morphology and functions through the optimized balance between the mitochondrial fusion and division. Here we report a novel role of mitochondrial dynamics in controlling the number of ER-mitochondria encounter structure (ERMES) clusters in a yeast cell. Loss of mitochondrial fusion or division caused the increased or decreased number, respectively, of ERMES foci observed in cells. ERMES complexes, therefore, appear to cluster with each other and mitochondrial division may inhibit undesired ERMES hyper-clustering. Furthermore, our microscopic analyses suggest that ER stress induces dissociation of ERMES clusters, increasing the number of ERMES foci even in the absence of Ire1 and Hac1, which are essential factors for the UPR response. Interestingly, we found that ER stress leads to expansion of both the ER and mitochondrial membranes in an ERMES function-dependent manner. These findings imply that a cell is equipped with two independent regulatory mechanisms controlling the number of ER-mitochondria contact sites to meet the cellular as well as environmental demands.